Objective: The normal reference range for the anion gap (AG) has recently been questioned by several authors. Lowering the upper limit of normal of the AG has been found to be more sensitive in predicting elevated lactate in critically ill adults. The objectives of this study are i) to define a new upper limit of normal of the AG in a study population of healthy adult volunteers, ii) to determine the sensitivity, specificity, the positive predictive value and the negative predictive value of the new upper limit for AG in detecting elevated lactate in critically ill children and to compare these results to the old upper limit of normal of AG (16 mmol/l), iii) to construct a receiver-operating-characteristic (ROC) curve for anion gap as a predictor of elevated lactate, iv) to determine the relationship between anion gap and serum lactate levels in critically ill patients.
Design: A prospective, cohort study.
Setting: Paediatric Intensive Care Unit of a University Hospital.
Subjects: Part I: Convenience sample of healthy adult volunteers to provide a reference range for anion gap calculation. Part II: Consecutive children admitted to the Paediatric Intensive Care Unit who had lactate levels measured for clinical reasons.
Measurements: Part I: Electrolytes and blood gases were measured from blood samples drawn from 25 adult volunteers. The reference range for AG was calculated using the equation, AG = Na - (Cl + HCO3). The upper limit of normal was calculated as mean + 2 SD. Part II: Eligible ICU patients were included in this study if they had lactate, electrolytes and blood gases obtained simultaneously. The AG was calculated as above. The new upper limit of normal AG was compared to an AG of 16 for diagnosing an elevated plasma lactate.
Results: The mean anion gap in the normal population was 9.4 +/- 1 mmol/l with 11 mmol/l being used as the new upper limit of normal. Thirty-six ICU patients had 189 arterial blood samples from which lactate, electrolytes and blood gas were measured simultaneously. The sensitivity, specificity, positive predictive value and negative predictive value of using an AG of 11 mmol/l as the upper limit of normal were 86%, 40%, 65% and 69% respectively, compared to 49%, 84%, 80% and 55% respectively using the upper limit of normal of AG of 16 mmol/l. The ROC curve supported lowering the upper limit of normal for the anion gap to predict an elevated lactate. There was a linear relationship between anion gap and serum lactate levels.
Conclusions: An AG of 11 mmol/l as the upper limit of normal has a higher sensitivity and higher negative predictive value but lower specificity and lower positive predictive value for detecting elevated lactate in critically ill children.